Infantile Tremor Syndrome or a Neurocutaneous Infantile B12 Deficiency (NIB) Syndrome?

To prospectively study the clinical and developmental profile; hematological profile and the B-12 status using multiple parameters in children with Infantile tremor syndrome (ITS). In this observational study (NCT02762682) (July 2015 through December 2016) children (and their mothers) with a clinical diagnosis of ITS were evaluated clinically; and development was assessed by CAPUTE scales. A complete blood count (CBC); peripheral blood smear examination; markers of vitamin B12 status (serum B12, homocysteine, folate); acylcarnitines [using Tandem mass spectrometry (TMS)] and urine methylmalonic acid (MMA) [Gas chromatography mass spectrometry (GCMS)] were estimated. A control group of children and their mothers were sampled for comparison. A total of 286 individuals were enrolled for this study. One-hundred-ten children with ITS were screened and 92 (20 with tremors; age 12.7 ± 5 mo, 61 boys) children and their mothers were enrolled. Fifty-one children and their mothers were enrolled as controls. The median clinical linguistic & auditory milestone-developmental quotient (CLAM-DQ) was 32 (IQR 20.6-45.5) and median cognitive adaptive test-developmental quotient (CAT-DQ) was 36.2 (IQR 18.7-49.0). All babies except 9 (ovo-veg) had vegetarian mothers. Head circumference below 2 SD (WHO standards) was seen in 84% and below 3 SD in 58%. The CBC findings were; Hb- 8.3 ± 1.6 g/dl, Thrombocytopenia-29 (32%), mean corpuscular volume (MCV)- 92.2 ± 13.4, MCV- more than 95 fL-38(42%), Red cell distribution width (RDW)- 21.6 ± 6.5, and macrocytes on peripheral smear in 68%. In 89 (97%) out of 92 children had laboratory features of deficient B12 status. Two-thirds of the mothers also had evidence of B12 deficiency. ITS is, in all likelihood is a consequence of vitamin B12 defeciency. It has a significant impact on head growth and development of affected infants.